All auditory information used for sound localization ascends through the brainstem auditory nuclei. We will use physiological and theoretical approaches to understand how multidimensional features of sound, relevant to sound localization, are processed and encoded in the avian auditory brainstem. A primary advantage of using barn owls for the exploration of auditory processing is the substantial body of behavioral, anatomical and neurophysiological work that has elucidated the mechanisms of sound localization. The main cues owls use to compute sound direction are the interaural level difference (ILD) and the interaural time difference (ITD). Unlike mammals, owls use ILD to determine the vertical coordinate of the sound source and ITD to determine the horizontal coordinate. Two independent brainstem pathways process ITD and ILD and converge in the midbrain, where a spatiotopic map of auditory space emerges. Activity of neurons in the map precedes, and stimulation evokes, a head-orienting response towards the sound source. Thus, in barn owls, the neural algorithm for sound localization can be viewed as a system in which two input variables (ITD and ILD) are processed in parallel in order to control two output variables (horizontal and vertical coordinates of head saccades). We have used theoretical models to describe the neural responses that encode spatial information in the owl's auditory system. This approach has guided our experiments and aided the interpretation of our findings. Behavioral experiments in humans have used a similar approach to sound localization. However, due to a lack of neural data in humans, the predictive power of models of sound localization with regard to the neural bases of behavior has been a persistent question. Our studies in barn owls address this issue by investigating the mechanism of neural computations that are fundamental to models developed for human sound localization. This proposal is organized around three primary questions: 1) What are the computational primitives of auditory-space processing in the owl's brainstem? 2) How is spectrotemporal information encoded, transmitted and processed in parallel with spatial information? 3) What fundamental changes in information coding occur at the crossroads between the auditory midbrain and forebrain? We will address these questions using a wide range of strategies and techniques - intracellular in vivo recordings, cell-attached recording in vivo, multi-neuron tetrode recording, and modeling - which will make our approach interdisciplinary and of broad scope. Our research seeks to understand the function of the auditory brainstem and midbrain. In doing so, we will identify the types of information that are available to upstream nuclei and show how this information is encoded. A comprehensive approach to information processing in the auditory brainstem has the potential to provide new avenues for better understanding disorders of the central auditory system and cognitive impairments involving hearing. By linking biology and engineering, mathematical formulations of brain processes can advance technology related to robotics and neural prosthetics. Cochlear implants that provide encoding of stimuli in ways that are more biologically relevant can be built, while devices acting downstream of the cochlea could aid patients with compromised or non-functional auditory nerves. By its differences and similarities with other species, the avian brain provides an excellent model system to define fundamental properties of neural processing and neural coding. PUBLIC HEALTH RELEVANCE: The proposed research will test hypotheses based on human models, of how the auditory system computes sound direction. This approach has the potential of providing new avenues for better understanding disorders of the central auditory system and cognitive impairments involving hearing. By linking biology and engineering, mathematical formulations of brain processes can advance technology related to artificial intelligence and neural prosthetics; smarter cochlear implants can be built, as well as devices acting downstream of the cochlea could aid patients with compromised or non-functional auditory nerves.